With increasing maternal age, there is an exponential increase in the frequency of children born with chromosomal disorders. A mouse model has been utilized to examine the mechanisms of this maternal age effect. The frequency of chromosomally abnormal embryos obtained from retired breeders (8+ months old) was significantly greater than that obtained from young (3-5 month old) females (32/244 (13 percent) vs. 5/229 (2 percent)). The genetic component of this maternal age effect was examined by measuring the frequencies of chromosomally abnormal fetuses derived from retired breeders of seveal inbred mouse strains (A/J, C3H, C57B1/6, CBA). In each of these inbred strains, a significant maternal age-related increase in chromosomally abnormal embryos was observed, indicating that simple genetic factors may not play an important role in the maternal age effect. The immunological component of the maternal age effect was analyzed by inducing immune incompetence in A/J mice by thymectomy and then determining the frequency of chromosomally abnormal embryos in old thymectomized females. The results revealed no difference in the frequencies of chromosomally abnormal embryos derived from thymectomized animals when compared to age-matched controls (17.1 percent vs. 16.7 percent). Studies are currently in progress to examine other proposed etiologic agents for the maternal age effect as well as to examine chromosomally aneuploidy as a function of aging in paternal gametes (sperm).